Pub Date : 2025-01-06Epub Date: 2024-12-06DOI: 10.1016/j.cub.2024.10.079
Gabriella J Spatola, Tatiana R Feuerborn, Jennifer A Betz, Reuben M Buckley, Gary K Ostrander, Emily V Dutrow, Alberto Velez, C Miguel Pinto, Alex C Harris, Jessica M Hale, Bruce D Barnett, Timothy A Mousseau, Elaine A Ostrander
Free-breeding dogs have occupied the Galápagos Islands at least since the 1830s; however, it was not until the 1900s that dog populations grew substantially, endangering wildlife and spreading disease.1,2,3,4 In 1981, efforts to control the population size of free-roaming dogs began.1 Yet, there exist large free-roaming dog populations on the islands of Isabela and Santa Cruz whose ancestry has never been assessed on a genome-wide scale. We thus performed a complete genomic analysis of the current Galápagos dog population, as well as historical Galápagos dogs sampled between 1969 and 2003, testing for population structure, admixture, and shared ancestry. Our dataset included samples from 187 modern and six historical Galápagos dogs, together with whole-genome sequences from over 2,000 modern purebred and village dogs. Our results indicate that modern Galápagos dogs are recently admixed with purebred dogs but show no evidence of a population bottleneck related to the culling. Additionally, identity-by-descent analyses reveal evidence of shared shepherd-dog ancestry in the historical dogs. Overall, our results demonstrate that the 1980s culling of dogs was ineffective in controlling population size and did little to reduce genetic diversity, instead producing a stable and expanding population with genomic signatures of modern purebred dogs. The insights from this study can be used to improve population control strategies for the Galápagos Islands and other endangered endemic communities.
{"title":"Genomic reconstruction reveals impact of population management strategies on modern Galápagos dogs.","authors":"Gabriella J Spatola, Tatiana R Feuerborn, Jennifer A Betz, Reuben M Buckley, Gary K Ostrander, Emily V Dutrow, Alberto Velez, C Miguel Pinto, Alex C Harris, Jessica M Hale, Bruce D Barnett, Timothy A Mousseau, Elaine A Ostrander","doi":"10.1016/j.cub.2024.10.079","DOIUrl":"10.1016/j.cub.2024.10.079","url":null,"abstract":"<p><p>Free-breeding dogs have occupied the Galápagos Islands at least since the 1830s; however, it was not until the 1900s that dog populations grew substantially, endangering wildlife and spreading disease.<sup>1</sup><sup>,</sup><sup>2</sup><sup>,</sup><sup>3</sup><sup>,</sup><sup>4</sup> In 1981, efforts to control the population size of free-roaming dogs began.<sup>1</sup> Yet, there exist large free-roaming dog populations on the islands of Isabela and Santa Cruz whose ancestry has never been assessed on a genome-wide scale. We thus performed a complete genomic analysis of the current Galápagos dog population, as well as historical Galápagos dogs sampled between 1969 and 2003, testing for population structure, admixture, and shared ancestry. Our dataset included samples from 187 modern and six historical Galápagos dogs, together with whole-genome sequences from over 2,000 modern purebred and village dogs. Our results indicate that modern Galápagos dogs are recently admixed with purebred dogs but show no evidence of a population bottleneck related to the culling. Additionally, identity-by-descent analyses reveal evidence of shared shepherd-dog ancestry in the historical dogs. Overall, our results demonstrate that the 1980s culling of dogs was ineffective in controlling population size and did little to reduce genetic diversity, instead producing a stable and expanding population with genomic signatures of modern purebred dogs. The insights from this study can be used to improve population control strategies for the Galápagos Islands and other endangered endemic communities.</p>","PeriodicalId":11359,"journal":{"name":"Current Biology","volume":" ","pages":"208-216.e5"},"PeriodicalIF":8.1,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11706705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-06DOI: 10.1016/j.cub.2024.12.022
Luca Troman, Ella de Gaulejac, Abin Biswas, Jennifer Stiens, Benno Kuropka, Carolyn A Moores, Simone Reber
Cellular processes are remarkably effective across diverse temperature ranges, even with highly conserved proteins. In the context of the microtubule cytoskeleton, which is critically involved in a wide range of cellular activities, this is particularly striking, as tubulin is one of the most conserved proteins while microtubule dynamic instability is highly temperature sensitive. Here, we leverage the diversity of natural tubulin variants from three closely related frog species that live at different temperatures. We determine the microtubule structure across all three species at between 3.0 and 3.6 Å resolution by cryo-electron microscopy and find small differences at the β-tubulin lateral interactions. Using in vitro reconstitution assays and quantitative biochemistry, we show that tubulin's free energy scales inversely with temperature. The observed weakening of lateral contacts and the low apparent activation energy for tubulin incorporation provide an explanation for the overall stability and higher growth rates of microtubules in cold-adapted frog species. This study thus broadens our conceptual framework for understanding microtubule dynamics and provides insights into how conserved cellular processes are tailored to different ecological niches.
即使是高度保守的蛋白质,在不同的温度范围内,细胞过程也具有显著的效力。微管细胞骨架参与了广泛的细胞活动,这一点尤其引人注目,因为微管蛋白是最保守的蛋白质之一,而微管的动态不稳定性对温度高度敏感。在这里,我们利用了生活在不同温度下的三种近缘蛙类的天然微管蛋白变体的多样性。我们通过低温电子显微镜以 3.0 至 3.6 Å 的分辨率确定了所有三个物种的微管结构,并发现了β-微管蛋白横向相互作用的微小差异。通过体外重组试验和定量生物化学研究,我们发现管蛋白的自由能与温度成反比。观察到的侧向接触减弱和管蛋白结合的表面活化能较低,为适应低温的青蛙物种微管的整体稳定性和较高生长率提供了解释。因此,这项研究拓宽了我们理解微管动力学的概念框架,并为我们深入了解保守的细胞过程如何适应不同的生态位提供了启示。
{"title":"Mechanistic basis of temperature adaptation in microtubule dynamics across frog species.","authors":"Luca Troman, Ella de Gaulejac, Abin Biswas, Jennifer Stiens, Benno Kuropka, Carolyn A Moores, Simone Reber","doi":"10.1016/j.cub.2024.12.022","DOIUrl":"https://doi.org/10.1016/j.cub.2024.12.022","url":null,"abstract":"<p><p>Cellular processes are remarkably effective across diverse temperature ranges, even with highly conserved proteins. In the context of the microtubule cytoskeleton, which is critically involved in a wide range of cellular activities, this is particularly striking, as tubulin is one of the most conserved proteins while microtubule dynamic instability is highly temperature sensitive. Here, we leverage the diversity of natural tubulin variants from three closely related frog species that live at different temperatures. We determine the microtubule structure across all three species at between 3.0 and 3.6 Å resolution by cryo-electron microscopy and find small differences at the β-tubulin lateral interactions. Using in vitro reconstitution assays and quantitative biochemistry, we show that tubulin's free energy scales inversely with temperature. The observed weakening of lateral contacts and the low apparent activation energy for tubulin incorporation provide an explanation for the overall stability and higher growth rates of microtubules in cold-adapted frog species. This study thus broadens our conceptual framework for understanding microtubule dynamics and provides insights into how conserved cellular processes are tailored to different ecological niches.</p>","PeriodicalId":11359,"journal":{"name":"Current Biology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142969962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-06Epub Date: 2024-12-03DOI: 10.1016/j.cub.2024.10.078
Alexandra C Nowlan, Jane Choe, Hoda Tromblee, Clancy Kelahan, Karin Hellevik, Stephen D Shea
Social encounters are inherently multisensory events, yet how and where social cues of distinct sensory modalities merge and interact in the brain is poorly understood. When their pups wander away from the nest, mother mice use a combination of vocal and olfactory signals emitted by the pups to locate and retrieve them. Previous work revealed the emergence of multisensory interactions in the auditory cortex (AC) of both dams and virgins who cohabitate with pups ("surrogates"). Here, we identify a neural pathway that relays information about odors to the AC to be integrated with responses to sound. We found that a scattered population of glutamatergic neurons in the basal amygdala (BA) projects to the AC and responds to odors, including the smell of pups. These neurons exhibit increased activity when the female is searching for pups that terminates upon contact. Finally, we show that selective optogenetic activation of BA-AC neurons modulates responses to pup calls, and that this modulation switches from predominantly suppressive to predominantly excitatory after maternal experience. This supports an underappreciated role for the amygdala in directly shaping sensory representations in an experience-dependent manner. We propose that the BA-AC pathway supports integration of olfaction and audition to facilitate maternal care and speculate that it may carry valence information to the AC.
{"title":"Multisensory integration of social signals by a pathway from the basal amygdala to the auditory cortex in maternal mice.","authors":"Alexandra C Nowlan, Jane Choe, Hoda Tromblee, Clancy Kelahan, Karin Hellevik, Stephen D Shea","doi":"10.1016/j.cub.2024.10.078","DOIUrl":"10.1016/j.cub.2024.10.078","url":null,"abstract":"<p><p>Social encounters are inherently multisensory events, yet how and where social cues of distinct sensory modalities merge and interact in the brain is poorly understood. When their pups wander away from the nest, mother mice use a combination of vocal and olfactory signals emitted by the pups to locate and retrieve them. Previous work revealed the emergence of multisensory interactions in the auditory cortex (AC) of both dams and virgins who cohabitate with pups (\"surrogates\"). Here, we identify a neural pathway that relays information about odors to the AC to be integrated with responses to sound. We found that a scattered population of glutamatergic neurons in the basal amygdala (BA) projects to the AC and responds to odors, including the smell of pups. These neurons exhibit increased activity when the female is searching for pups that terminates upon contact. Finally, we show that selective optogenetic activation of BA-AC neurons modulates responses to pup calls, and that this modulation switches from predominantly suppressive to predominantly excitatory after maternal experience. This supports an underappreciated role for the amygdala in directly shaping sensory representations in an experience-dependent manner. We propose that the BA-AC pathway supports integration of olfaction and audition to facilitate maternal care and speculate that it may carry valence information to the AC.</p>","PeriodicalId":11359,"journal":{"name":"Current Biology","volume":" ","pages":"36-49.e4"},"PeriodicalIF":8.1,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142779640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-06Epub Date: 2024-12-04DOI: 10.1016/j.cub.2024.10.069
Stephanie N Caty, Aurora Alvarez-Buylla, Cooper Vasek, Elicio E Tapia, Nora A Martin, Theresa McLaughlin, Chloe L Golde, Peter K Weber, Xavier Mayali, Luis A Coloma, Megan M Morris, Lauren A O'Connell
Shifts in host-associated microbiomes can impact both host and microbes.1,2,3,4,5,6 It is of interest to understand how perturbations, like the introduction of exogenous chemicals,7,8,9,10,11,12,13 impact microbiomes. In poison frogs (family Dendrobatidae), the skin microbiome is exposed to alkaloids that the frogs sequester for defense.14,15,16,17,18,19 These alkaloids are antimicrobial20,21,22; however, their effect on the frogs' skin microbiome is unknown. To test this, we characterized microbial communities from field-collected dendrobatid frogs. Then, we conducted a laboratory experiment to monitor the effect of the alkaloid decahydroquinoline (DHQ) on the microbiome of two frog species with contrasting alkaloid loads in nature. In both datasets, we found that alkaloid-exposed microbiomes were more phylogenetically diverse, with an increase in diversity among rare taxa. To better understand the isolate-specific response to alkaloids, we cultured microbial isolates from poison frog skin and found that many isolates exhibited enhanced growth or were not impacted by the addition of DHQ. To further explore the microbial response to alkaloids, we sequenced the metagenomes from high- and low-alkaloid frogs and observed a greater diversity of genes associated with nitrogen and carbon metabolism in high-alkaloid frogs. From these data, we hypothesized that some strains may metabolize the alkaloids. We used stable isotope tracing coupled to nanoSIMS (nanoscale secondary ion mass spectrometry), which supported the idea that some of these isolates are able to metabolize DHQ. Together, these data suggest that poison frog alkaloids open new niches for skin-associated microbes with specific adaptations, such as alkaloid metabolism, that enable survival in this environment.
{"title":"Alkaloids are associated with increased microbial diversity and metabolic function in poison frogs.","authors":"Stephanie N Caty, Aurora Alvarez-Buylla, Cooper Vasek, Elicio E Tapia, Nora A Martin, Theresa McLaughlin, Chloe L Golde, Peter K Weber, Xavier Mayali, Luis A Coloma, Megan M Morris, Lauren A O'Connell","doi":"10.1016/j.cub.2024.10.069","DOIUrl":"10.1016/j.cub.2024.10.069","url":null,"abstract":"<p><p>Shifts in host-associated microbiomes can impact both host and microbes.<sup>1</sup><sup>,</sup><sup>2</sup><sup>,</sup><sup>3</sup><sup>,</sup><sup>4</sup><sup>,</sup><sup>5</sup><sup>,</sup><sup>6</sup> It is of interest to understand how perturbations, like the introduction of exogenous chemicals,<sup>7</sup><sup>,</sup><sup>8</sup><sup>,</sup><sup>9</sup><sup>,</sup><sup>10</sup><sup>,</sup><sup>11</sup><sup>,</sup><sup>12</sup><sup>,</sup><sup>13</sup> impact microbiomes. In poison frogs (family Dendrobatidae), the skin microbiome is exposed to alkaloids that the frogs sequester for defense.<sup>14</sup><sup>,</sup><sup>15</sup><sup>,</sup><sup>16</sup><sup>,</sup><sup>17</sup><sup>,</sup><sup>18</sup><sup>,</sup><sup>19</sup> These alkaloids are antimicrobial<sup>20</sup><sup>,</sup><sup>21</sup><sup>,</sup><sup>22</sup>; however, their effect on the frogs' skin microbiome is unknown. To test this, we characterized microbial communities from field-collected dendrobatid frogs. Then, we conducted a laboratory experiment to monitor the effect of the alkaloid decahydroquinoline (DHQ) on the microbiome of two frog species with contrasting alkaloid loads in nature. In both datasets, we found that alkaloid-exposed microbiomes were more phylogenetically diverse, with an increase in diversity among rare taxa. To better understand the isolate-specific response to alkaloids, we cultured microbial isolates from poison frog skin and found that many isolates exhibited enhanced growth or were not impacted by the addition of DHQ. To further explore the microbial response to alkaloids, we sequenced the metagenomes from high- and low-alkaloid frogs and observed a greater diversity of genes associated with nitrogen and carbon metabolism in high-alkaloid frogs. From these data, we hypothesized that some strains may metabolize the alkaloids. We used stable isotope tracing coupled to nanoSIMS (nanoscale secondary ion mass spectrometry), which supported the idea that some of these isolates are able to metabolize DHQ. Together, these data suggest that poison frog alkaloids open new niches for skin-associated microbes with specific adaptations, such as alkaloid metabolism, that enable survival in this environment.</p>","PeriodicalId":11359,"journal":{"name":"Current Biology","volume":" ","pages":"187-197.e8"},"PeriodicalIF":8.1,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142784561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-06Epub Date: 2024-12-05DOI: 10.1016/j.cub.2024.10.075
Guifré Torruella, Luis Javier Galindo, David Moreira, Purificación López-García
Eukaryotes evolved from prokaryotic predecessors in the early Proterozoic1,2 and radiated from their already complex last common ancestor,3 diversifying into several supergroups with unresolved deep evolutionary connections.4 They evolved extremely diverse lifestyles, playing crucial roles in the carbon cycle.5,6 Heterotrophic flagellates are arguably the most diverse eukaryotes4,7,8,9 and often occupy basal positions in phylogenetic trees. However, many of them remain undersampled4,10 and/or incertae sedis.4,11,12,13,14,15,16,17,18 Progressive improvement of phylogenomic methods and a wider protist sampling have reshaped and consolidated major clades in the eukaryotic tree.13,14,15,16,17,18,19 This is illustrated by the Opimoda,14 one of the largest eukaryotic supergroups (Amoebozoa, Ancyromonadida, Apusomonadida, Breviatea, CRuMs [Collodictyon-Rigifila-Mantamonas], Malawimonadida, and Opisthokonta-including animals and fungi).4,14,19,20,21,22 However, their deepest evolutionary relationships still remain uncertain. Here, we sequenced transcriptomes of poorly studied flagellates23,24 (14 apusomonads,25,26 7 ancyromonads,27 and 1 cultured Mediterranean strain of Meteora sporadica17) and conducted comprehensive phylogenomics analyses with an expanded taxon sampling of early-branching protists. Our findings support the monophyly of Opimoda, with CRuMs being sister to the Amorphea (amoebozoans, breviates, apusomonads, and opisthokonts) and ancyromonads and malawimonads forming a moderately supported clade. By mapping key complex phenotypic traits onto this phylogenetic framework, we infer an opimodan biflagellate ancestor with an excavate-like feeding groove, which ancyromonads subsequently lost. Although breviates and apusomonads retained the ancestral biflagellate state, some early-diverging Amorphea lost one or both flagella, facilitating the evolution of amoeboid morphologies, novel feeding modes, and palintomic cell division resulting in multinucleated cells. These innovations likely facilitated the subsequent evolution of fungal and metazoan multicellularity.
{"title":"Phylogenomics of neglected flagellated protists supports a revised eukaryotic tree of life.","authors":"Guifré Torruella, Luis Javier Galindo, David Moreira, Purificación López-García","doi":"10.1016/j.cub.2024.10.075","DOIUrl":"10.1016/j.cub.2024.10.075","url":null,"abstract":"<p><p>Eukaryotes evolved from prokaryotic predecessors in the early Proterozoic<sup>1</sup><sup>,</sup><sup>2</sup> and radiated from their already complex last common ancestor,<sup>3</sup> diversifying into several supergroups with unresolved deep evolutionary connections.<sup>4</sup> They evolved extremely diverse lifestyles, playing crucial roles in the carbon cycle.<sup>5</sup><sup>,</sup><sup>6</sup> Heterotrophic flagellates are arguably the most diverse eukaryotes<sup>4</sup><sup>,</sup><sup>7</sup><sup>,</sup><sup>8</sup><sup>,</sup><sup>9</sup> and often occupy basal positions in phylogenetic trees. However, many of them remain undersampled<sup>4</sup><sup>,</sup><sup>10</sup> and/or incertae sedis.<sup>4</sup><sup>,</sup><sup>11</sup><sup>,</sup><sup>12</sup><sup>,</sup><sup>13</sup><sup>,</sup><sup>14</sup><sup>,</sup><sup>15</sup><sup>,</sup><sup>16</sup><sup>,</sup><sup>17</sup><sup>,</sup><sup>18</sup> Progressive improvement of phylogenomic methods and a wider protist sampling have reshaped and consolidated major clades in the eukaryotic tree.<sup>13</sup><sup>,</sup><sup>14</sup><sup>,</sup><sup>15</sup><sup>,</sup><sup>16</sup><sup>,</sup><sup>17</sup><sup>,</sup><sup>18</sup><sup>,</sup><sup>19</sup> This is illustrated by the Opimoda,<sup>14</sup> one of the largest eukaryotic supergroups (Amoebozoa, Ancyromonadida, Apusomonadida, Breviatea, CRuMs [Collodictyon-Rigifila-Mantamonas], Malawimonadida, and Opisthokonta-including animals and fungi).<sup>4</sup><sup>,</sup><sup>14</sup><sup>,</sup><sup>19</sup><sup>,</sup><sup>20</sup><sup>,</sup><sup>21</sup><sup>,</sup><sup>22</sup> However, their deepest evolutionary relationships still remain uncertain. Here, we sequenced transcriptomes of poorly studied flagellates<sup>23</sup><sup>,</sup><sup>24</sup> (14 apusomonads,<sup>25</sup><sup>,</sup><sup>26</sup> 7 ancyromonads,<sup>27</sup> and 1 cultured Mediterranean strain of Meteora sporadica<sup>17</sup>) and conducted comprehensive phylogenomics analyses with an expanded taxon sampling of early-branching protists. Our findings support the monophyly of Opimoda, with CRuMs being sister to the Amorphea (amoebozoans, breviates, apusomonads, and opisthokonts) and ancyromonads and malawimonads forming a moderately supported clade. By mapping key complex phenotypic traits onto this phylogenetic framework, we infer an opimodan biflagellate ancestor with an excavate-like feeding groove, which ancyromonads subsequently lost. Although breviates and apusomonads retained the ancestral biflagellate state, some early-diverging Amorphea lost one or both flagella, facilitating the evolution of amoeboid morphologies, novel feeding modes, and palintomic cell division resulting in multinucleated cells. These innovations likely facilitated the subsequent evolution of fungal and metazoan multicellularity.</p>","PeriodicalId":11359,"journal":{"name":"Current Biology","volume":" ","pages":"198-207.e4"},"PeriodicalIF":8.1,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-06Epub Date: 2024-12-02DOI: 10.1016/j.cub.2024.11.006
Shaun F Morrison, Georgina Cano, Shelby L Hernan, Pierfrancesco Chiavetta, Domenico Tupone
To maintain core body temperature in mammals, CNS thermoregulatory networks respond to cold exposure by increasing brown adipose tissue and shivering thermogenesis. However, in hibernation or torpor, this canonical thermoregulatory response is replaced by a new, emerging paradigm, thermoregulatory inversion (TI), an alternative homeostatic state in which cold exposure inhibits thermogenesis and warm exposure stimulates thermogenesis. Here, we demonstrate that in the non-torpid rat, either exclusion of the canonical thermoregulatory integrator in the preoptic hypothalamus or inhibition of neurons in the ventromedial periventricular area (VMPeA) induces the TI state through an alternative thermoregulatory pathway. Within this pathway, we have identified a dynorphinergic input to the dorsomedial hypothalamus from the dorsolateral parabrachial nucleus that plays a critical role in mediating the cold-evoked inhibition of thermogenesis during TI. Our results reveal a novel thermosensory reflex circuit within the mammalian CNS thermoregulatory pathways and support the potential for pharmacologically inducing the TI state to elicit therapeutic hypothermia in non-hibernating species, including humans.
{"title":"Inhibition of the hypothalamic ventromedial periventricular area activates a dynorphin pathway-dependent thermoregulatory inversion in rats.","authors":"Shaun F Morrison, Georgina Cano, Shelby L Hernan, Pierfrancesco Chiavetta, Domenico Tupone","doi":"10.1016/j.cub.2024.11.006","DOIUrl":"10.1016/j.cub.2024.11.006","url":null,"abstract":"<p><p>To maintain core body temperature in mammals, CNS thermoregulatory networks respond to cold exposure by increasing brown adipose tissue and shivering thermogenesis. However, in hibernation or torpor, this canonical thermoregulatory response is replaced by a new, emerging paradigm, thermoregulatory inversion (TI), an alternative homeostatic state in which cold exposure inhibits thermogenesis and warm exposure stimulates thermogenesis. Here, we demonstrate that in the non-torpid rat, either exclusion of the canonical thermoregulatory integrator in the preoptic hypothalamus or inhibition of neurons in the ventromedial periventricular area (VMPeA) induces the TI state through an alternative thermoregulatory pathway. Within this pathway, we have identified a dynorphinergic input to the dorsomedial hypothalamus from the dorsolateral parabrachial nucleus that plays a critical role in mediating the cold-evoked inhibition of thermogenesis during TI. Our results reveal a novel thermosensory reflex circuit within the mammalian CNS thermoregulatory pathways and support the potential for pharmacologically inducing the TI state to elicit therapeutic hypothermia in non-hibernating species, including humans.</p>","PeriodicalId":11359,"journal":{"name":"Current Biology","volume":" ","pages":"59-76.e4"},"PeriodicalIF":8.1,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11706707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Human intelligence is characterized by the remarkable ability to solve complex problems by planning a sequence of actions that takes us from an initial state to a desired goal state. Quantifying and comparing problem-solving capabilities across species and finding their evolutionary roots are critical for understanding how the brain carries out this intricate process. We introduce the Language of Problem Solving (LoPS) model as a novel quantitative framework that investigates the structure of problem-solving behavior through a language model. We applied the model to an adapted classic Pac-Man game as a cross-species behavioral paradigm to test both humans and macaque monkeys. The LoPS model extracted the latent structure, or grammar, embedded in the agents' gameplay, revealing the non-Markovian temporal dependency structure of their problem-solving behavior and the hierarchical structures of problem solving in both species. The complexity of LoPS grammar correlated with individuals' game performance and reflected the difference in problem-solving capacity between humans and monkeys. Both species evolved their LoPS grammars during learning, progressing from simpler to more complex ones, suggesting that the structure of problem solving is not fixed but evolves to support more sophisticated and efficient problem solving. Our study provides insights into how humans and monkeys break down problem solving into compositional units and navigate complex tasks, deepening our understanding of human intelligence and its evolution and establishing a foundation for future investigations of the neural mechanisms of problem solving.
{"title":"A language model of problem solving in humans and macaque monkeys.","authors":"Qianli Yang, Zhihua Zhu, Ruoguang Si, Yunwei Li, Jiaxiang Zhang, Tianming Yang","doi":"10.1016/j.cub.2024.10.074","DOIUrl":"10.1016/j.cub.2024.10.074","url":null,"abstract":"<p><p>Human intelligence is characterized by the remarkable ability to solve complex problems by planning a sequence of actions that takes us from an initial state to a desired goal state. Quantifying and comparing problem-solving capabilities across species and finding their evolutionary roots are critical for understanding how the brain carries out this intricate process. We introduce the Language of Problem Solving (LoPS) model as a novel quantitative framework that investigates the structure of problem-solving behavior through a language model. We applied the model to an adapted classic Pac-Man game as a cross-species behavioral paradigm to test both humans and macaque monkeys. The LoPS model extracted the latent structure, or grammar, embedded in the agents' gameplay, revealing the non-Markovian temporal dependency structure of their problem-solving behavior and the hierarchical structures of problem solving in both species. The complexity of LoPS grammar correlated with individuals' game performance and reflected the difference in problem-solving capacity between humans and monkeys. Both species evolved their LoPS grammars during learning, progressing from simpler to more complex ones, suggesting that the structure of problem solving is not fixed but evolves to support more sophisticated and efficient problem solving. Our study provides insights into how humans and monkeys break down problem solving into compositional units and navigate complex tasks, deepening our understanding of human intelligence and its evolution and establishing a foundation for future investigations of the neural mechanisms of problem solving.</p>","PeriodicalId":11359,"journal":{"name":"Current Biology","volume":" ","pages":"11-20.e10"},"PeriodicalIF":8.1,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142779634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-06Epub Date: 2024-12-03DOI: 10.1016/j.cub.2024.10.067
Merybeth Fernandez Triana, Felipe Andreazza, Nadia Melo, Rickard Ignell, Ali Afify, Yuan Li, Dan-Dan Zhang, Christopher J Potter, Ke Dong, Marcus C Stensmyr
Humanity has long battled mosquitoes and the diseases they transmit-a struggle intensified by climate change and globalization, which have expanded mosquito ranges and the spread of associated diseases.1 Additionally, widespread insecticide resistance has reduced the efficacy of current control methods, necessitating new solutions.2,3 Nootkatone, a natural compound found in grapefruit, shows promise as both a mosquito repellent and an insecticide.4,5 However, its mechanism of action remains unclear. Our study demonstrates that nootkatone acts as a potent spatial and contact repellent against multiple mosquito species. Nootkatone-induced spatial aversion, which is influenced by human odor, is in Aedes aegypti partially mediated by Orco- and ionotropic receptor (IR)-positive neurons, while contact aversion is robust and likely mediated via the proboscis and independent of TRPA1 and IRs. We further find that nootkatone potentiates γ-aminobutyric acid (GABA)-mediated signaling by modulating the broadly expressed major insect GABA-gated chloride channel resistant to dieldrin (Rdl). At low doses, the chemosensory-mediated spatial and contact repellency is likely strengthened by nootkatone's disruption of synaptic transmission in select mosquito sensory neurons. At higher doses, nootkatone induces paralysis and death, presumably through broad-range synaptic transmission disruption. These findings reveal nootkatone's unique mode of action and highlight its potential as an effective mosquito control agent. Its dual role as a repellent and an insecticide, combined with low-to-no toxicity to humans and a pleasant smell, underscores nootkatone's promise as a future tool in mosquito control efforts.
{"title":"Grapefruit-derived nootkatone potentiates GABAergic signaling and acts as a dual-action mosquito repellent and insecticide.","authors":"Merybeth Fernandez Triana, Felipe Andreazza, Nadia Melo, Rickard Ignell, Ali Afify, Yuan Li, Dan-Dan Zhang, Christopher J Potter, Ke Dong, Marcus C Stensmyr","doi":"10.1016/j.cub.2024.10.067","DOIUrl":"10.1016/j.cub.2024.10.067","url":null,"abstract":"<p><p>Humanity has long battled mosquitoes and the diseases they transmit-a struggle intensified by climate change and globalization, which have expanded mosquito ranges and the spread of associated diseases.<sup>1</sup> Additionally, widespread insecticide resistance has reduced the efficacy of current control methods, necessitating new solutions.<sup>2</sup><sup>,</sup><sup>3</sup> Nootkatone, a natural compound found in grapefruit, shows promise as both a mosquito repellent and an insecticide.<sup>4</sup><sup>,</sup><sup>5</sup> However, its mechanism of action remains unclear. Our study demonstrates that nootkatone acts as a potent spatial and contact repellent against multiple mosquito species. Nootkatone-induced spatial aversion, which is influenced by human odor, is in Aedes aegypti partially mediated by Orco- and ionotropic receptor (IR)-positive neurons, while contact aversion is robust and likely mediated via the proboscis and independent of TRPA1 and IRs. We further find that nootkatone potentiates γ-aminobutyric acid (GABA)-mediated signaling by modulating the broadly expressed major insect GABA-gated chloride channel resistant to dieldrin (Rdl). At low doses, the chemosensory-mediated spatial and contact repellency is likely strengthened by nootkatone's disruption of synaptic transmission in select mosquito sensory neurons. At higher doses, nootkatone induces paralysis and death, presumably through broad-range synaptic transmission disruption. These findings reveal nootkatone's unique mode of action and highlight its potential as an effective mosquito control agent. Its dual role as a repellent and an insecticide, combined with low-to-no toxicity to humans and a pleasant smell, underscores nootkatone's promise as a future tool in mosquito control efforts.</p>","PeriodicalId":11359,"journal":{"name":"Current Biology","volume":" ","pages":"177-186.e6"},"PeriodicalIF":8.1,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142779637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-06DOI: 10.1016/j.cub.2024.11.073
Sebastian Klavinskis-Whiting, Emil Fristed, Yosef Singer, M Florencia Iacaruso, Andrew J King, Nicol S Harper
Neurons in primary visual cortex (V1) show a remarkable functional specificity in their pre- and postsynaptic partners. Recent work has revealed a variety of wiring biases describing how the short- and long-range connections of V1 neurons relate to their tuning properties. However, it is less clear whether these connectivity rules are based on some underlying principle of cortical organization. Here, we show that the functional specificity of V1 connections emerges naturally in a recurrent neural network optimized to predict upcoming sensory inputs for natural visual stimuli. This temporal prediction model reproduces the complex relationships between the connectivity of V1 neurons and their orientation and direction preferences, the tendency of highly connected neurons to respond more similarly to natural movies, and differences in the functional connectivity of excitatory and inhibitory V1 populations. Together, these findings provide a principled explanation for the functional and anatomical properties of early sensory cortex.
{"title":"Prediction of future input explains lateral connectivity in primary visual cortex.","authors":"Sebastian Klavinskis-Whiting, Emil Fristed, Yosef Singer, M Florencia Iacaruso, Andrew J King, Nicol S Harper","doi":"10.1016/j.cub.2024.11.073","DOIUrl":"https://doi.org/10.1016/j.cub.2024.11.073","url":null,"abstract":"<p><p>Neurons in primary visual cortex (V1) show a remarkable functional specificity in their pre- and postsynaptic partners. Recent work has revealed a variety of wiring biases describing how the short- and long-range connections of V1 neurons relate to their tuning properties. However, it is less clear whether these connectivity rules are based on some underlying principle of cortical organization. Here, we show that the functional specificity of V1 connections emerges naturally in a recurrent neural network optimized to predict upcoming sensory inputs for natural visual stimuli. This temporal prediction model reproduces the complex relationships between the connectivity of V1 neurons and their orientation and direction preferences, the tendency of highly connected neurons to respond more similarly to natural movies, and differences in the functional connectivity of excitatory and inhibitory V1 populations. Together, these findings provide a principled explanation for the functional and anatomical properties of early sensory cortex.</p>","PeriodicalId":11359,"journal":{"name":"Current Biology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142969966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-06DOI: 10.1016/j.cub.2024.11.067
Christophe Guérin, Anne-Betty N'Diaye, Laurène Gressin, Alex Mogilner, Manuel Théry, Laurent Blanchoin, Alexandra Colin
In cells, multiple actin networks coexist in a dynamic manner. These networks compete for a common pool of actin monomers and actin-binding proteins. Interestingly, all of these networks manage to coexist despite the strong competition for resources. Moreover, the coexistence of networks with various strengths is key to cell adaptation to external changes. However, a comprehensive view of how these networks coexist in this competitive environment, where resources are limited, is still lacking. To address this question, we used a reconstituted system, in closed microwells, consisting of beads propelled by actin polymerization or micropatterns functionalized with lipids capable of initiating polymerization close to a membrane. This system enabled us to build dynamic actin architectures, competing for a limited pool of proteins, over a period of hours. We demonstrated the importance of protein turnover for the coexistence of actin networks, showing that it ensures resource distribution between weak and strong networks. However, when competition becomes too intense, turnover alone is insufficient, leading to a selection process that favors the strongest networks. Consequently, we emphasize the importance of competition strength, which is defined by the turnover rate, the amount of available protein, and the number of competing structures. More generally, this work illustrates how turnover allows biological populations with various competition strengths to coexist despite resource constraints.
{"title":"Balancing limited resources in actin network competition.","authors":"Christophe Guérin, Anne-Betty N'Diaye, Laurène Gressin, Alex Mogilner, Manuel Théry, Laurent Blanchoin, Alexandra Colin","doi":"10.1016/j.cub.2024.11.067","DOIUrl":"https://doi.org/10.1016/j.cub.2024.11.067","url":null,"abstract":"<p><p>In cells, multiple actin networks coexist in a dynamic manner. These networks compete for a common pool of actin monomers and actin-binding proteins. Interestingly, all of these networks manage to coexist despite the strong competition for resources. Moreover, the coexistence of networks with various strengths is key to cell adaptation to external changes. However, a comprehensive view of how these networks coexist in this competitive environment, where resources are limited, is still lacking. To address this question, we used a reconstituted system, in closed microwells, consisting of beads propelled by actin polymerization or micropatterns functionalized with lipids capable of initiating polymerization close to a membrane. This system enabled us to build dynamic actin architectures, competing for a limited pool of proteins, over a period of hours. We demonstrated the importance of protein turnover for the coexistence of actin networks, showing that it ensures resource distribution between weak and strong networks. However, when competition becomes too intense, turnover alone is insufficient, leading to a selection process that favors the strongest networks. Consequently, we emphasize the importance of competition strength, which is defined by the turnover rate, the amount of available protein, and the number of competing structures. More generally, this work illustrates how turnover allows biological populations with various competition strengths to coexist despite resource constraints.</p>","PeriodicalId":11359,"journal":{"name":"Current Biology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142964276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}